Machine learning for the micropeptide encoded by LINC02381 regulates ferroptosis through the glucose transporter SLC2A10 in glioblastoma

Abstract

Glioblastoma (GBM) is the most common primary intracranial tumor in the central nervous system, and resistance to temozolomide is an important reason for the failure of GBM treatment. We screened out that Solute Carrier Family 2 Member 10 (SLC2A10) is significantly highly expressed in GBM with a poor prognosis, which is also enriched in the NF-E2 p45-related factor 2 (NRF2) signalling pathway. The NRF2 signalling pathway is an important defence mechanism against ferroptosis. SLC2A10 related LINC02381 is highly expressed in GBM, which is localized in the cytoplasm/exosomes, and LINC02381 encoded micropeptides are localized in the exosomes. The micropeptide encoded by LINC02381 may be a potential treatment strategy for GBM, but the underlying mechanism of its function is not precise yet. We put forward the hypothesis: “The micropeptide encoded by LINC02381 regulates ferroptosis through the glucose transporter SLC2A10 in GBM.” This study innovatively used machine learning for micropeptide to provide personalized diagnosis and treatment plans for precise treatment of GBM, thereby promoting the development of translational medicine. The study aimed to help find new disease diagnoses and prognostic biomarkers and provide a new strategy for experimental scientists to design the downstream validation experiments.

Multi‐omics analysis reveals the association between specific solute carrier proteins gene expression patterns and the immune suppressive microenvironment in glioma

“…We then validated our findings using qPCR experiments and spatial transcriptome data. Among these SLCs, SLC2A10 has been reported to be associated with ferroptosis in glioblastoma, 43 SLC47A1 has been demonstrated to mediate temozolomide resistance in glioblastoma, 44 while the functions of the other SLCs in glioblastoma remain unclear. Next, to enhance the prediction of prognosis for glioma patients, we established a risk scoring system based on these seven core SLCs.…”

“…to be associated with ferroptosis in glioblastoma, 43 In fact, our risk scoring system, which is based on the product of regression coefficients and expression levels, quantifies the distinct expression patterns of these seven SLCs in different patients.…”

Micropeptides: potential treatment strategies for cancer

“…Interestingly, Jiang et al found that LINC02381-aa, a micropeptide encoded by LINC02381, localizes to exosomes and may regulate iron concentration in GBM via the action of the glucose transporter SLC2A10 [ 114 ]. Furthermore, it was found that exosomal lncAKR1C2 can encode a microprotein with biological functions in recipient cells and promotes the expression of CPT1A by regulating YAP phosphorylation, which leads to enhanced fatty acid oxidation and ATP production.…”

Subcellular localization and relevant mechanisms of human cancer‐related micropeptides

“…In GBM, LINC02381 is highly expressed and localized in the cytoplasm, whereas its coding micropeptide is enriched in the exosome and promotes cell proliferation and growth by regulating ferroptosis. LINC02381‐aa 89 interacts with SLC2A10 and activates the NRF2 signaling pathway, which plays an important role in defending against ferroptosis. Furthermore, the presence of LINC02381‐aa in exosomes can be a potential antitumor therapy for targeting exosomes (Figure 3H).…”